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Showing 1 to 20 of 82 for “"NHEJ"”.
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Pathways of NHEJ at Dysfunctional Telomeres and Their Resolution
… the decision between non-homologous endjoining (NHEJ) and homologous recombination (HR). Telomeres lacking the shelterin protein TRF2 have proven a versatile system for studying 53BP1 in DSB repair since 53BP1 protects dysfunctional telomeres from resection and promotes their mobility. Analysis …
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Cryo-EM as a Tool to Study the Diverse Interactome of Ku 70/80 in NHEJ and Beyond
… thesis focuses on Non-Homologous End Joining (NHEJ), one of the main DNA repair mechanisms in cells. NHEJ lies under the umbrella of the DNA Damage Response (DDR), a collection of cellular pathways that combat the tens of thousands DNA lesions a single cell experiences each day from both …
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Identification and characterization of novel genes involved in DNA double strand break repair process in the yeast Saccharomyces cerevisiae
… (HR) and Non-Homologous End Joining (NHEJ). Both pathways are highly conserved from yeast to human. HR requires a homologous region to repair the damage but in NHEJ, the break ends are ligated directly. In Saccharomyces cerevisiae, the key protein complexes of the NHEJ pathway are: …
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Investigating the regulation of DNA non-homologous end-joining through Ku70/80 interacting factors
… (HR) and non-homologous end-joining (NHEJ). Whilst the regulation of HR has been heavily investigated, the regulation of NHEJ remains to be fully explored. The aim of this thesis is to investigate the regulation of DNA NHEJ through interacting factors of the core NHEJ protein …
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Altered Kinetics of Non-Homologous End Joining Mediated DNA Repair in Mouse Models of Aging and Leukemia
… DSB are repaired by Non-homologous end joining (NHEJ). Unrepaired DSB can lead to genomic instability resulting in cell cycle arrest, apoptosis, and mutations. Thus, delineating this DNA repair process is important in understanding the molecular mechanisms of aging and malignant progression. B …
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Double-Strand Break Repair Pathways In Dna Structure-Induced Genetic Instability
… within each species. Non-homologous end-joining (NHEJ) is primed to repair DSBs in mammalian cells, while bacteria that lack NHEJ (such as E.coli), utilize homologous recombination (HR) to repair DSBs. To investigate the role of the error-prone NHEJ repair pathway in DNA structure-induced genetic …
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Development of Novel Technologies to Investigate DNA Double-Strand Break Repair Uncovers a Role for the ATM Kinase in Error-Free NHEJ with Implications for Neurodegenerative Diseases
… via error-free non-homologous end joining (EF-NHEJ), mutagenic end joining (mut-EJ), alternative end joining (alt-EJ), homologous recombination (HR), and single strand annealing (SSA) at a single break created within individual cells by CRISPR-Cas9. We demonstrate that DSB-Prism robustly …
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Nonhomologous end-joining: TDP1-mediated processing, ATM-mediated signaling
… separate features of nonhomologous end-joining (NHEJ) DNA repair: end processing, and DNA repair kinase signaling. DNA end processing was investigated in a mouse model of hereditary spinocerebellar ataxia with axonal neuropathy (SCAN1), a congenital neurodegenerative disease. SCAN1 is caused by a …
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Understanding The Roles of Non-Homologous End Joining and P53 After Dna Damage
… strand breaks is non-homologous end joining (NHEJ). Abrogating the NHEJ pathway leads to an accumulation of DNA damage in the lymphoid system that triggers p53-mediated apoptosis; complete deletion of p53 in this system leads to aggressive lymphomagenesis. Therefore, to study the effect of …
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Prediction and Investigation of Novel Proteins in DNA Double Stranded Break Repair
… (HR) and non-homologous end joining (NHEJ). HR requires a homologous sequence to repair DNA breaks, whereas NHEJ repair is achieved through direct ligation of the broken ends of DNA. The process of NHEJ involves three main protein complexes: Yku70/Yku80 initiates and stabilizes the DNA …
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Modulation of DNA repair pathway after CRISPR/Cas9 mediated Double Stranded Break
… repaired by either non-homologous end joining (NHEJ) or homologous recombination (HR), and the repair is commonly processed through NHEJ because it is the dominant repair pathway in most cell types. The goal of this study is to modulate DNA repair system of somatic cells to increase the …
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Determining molecular mechanisms of DNA Non-Homologous End Joining proteins
… and abasic sites. Non-homologous end joining (NHEJ) is a major pathway responsible for the repair of these complex breaks. Proteins involved in NHEJ include the Ku 70/80 heterodimer, DNA-PKcs, processing proteins including Artemis and DNA polymerases µ and λ, XRCC4, DNA ligase IV and XLF. The …
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DNA repair proteins Metnase and PARP1 regulate DNA integration
… (HR) and non-homologous end joining (NHEJ). In mammalian cells, NHEJ occurs more frequently than HR, possibly explains why random integration is more efficient than homology-directed integration or gene targeting. Proteins function in DSB repair pathways often engage in DNA …
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DNA-PKcs/ Artemis Complex in DNA Double-Strand-Break Repair: Cryo-EM and Biochemical Studies
… (HR) and non-homologous end joining (NHEJ). My PhD project focuses on NHEJ. Unlike HR, NHEJ is not limited by the cell cycle as it does not require a template for recombination. Also, NHEJ has been shown to be the preferred DSB repair pathway in higher eukaryotic organisms including …
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Development of Natural Cyclic Peptide Inhibitors of XRCC4/XLF Interaction for Radio-Sensitization of Breast Tumor Cells
… primary mechanism is non-homologous end joining (NHEJ) and the secondary mechanism is homologous recombination (HRR). Previous studies showed that breast tumor cells depend mainly on NHEJ for repairing induced DNA damage. XRCC4 and XLF are two essential proteins in the NHEJ process. The …
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Investigating Mechanisms of Telomere End-Protection
… (DSB) repair pathway non homologous end-joining (NHEJ). Mammalian Rap1 interacts with shelterin factor TRF2, to localize to telomeres, and human Rap1 is implicated in repressing NHEJ. Surprisingly, removal of Rap1 from telomeres revealed that mouse Rap1 was not required to inhibit NHEJ, but …
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The role of linker histone variant in double strand break repair
… pathway known as non-homologous end joining (NHEJ). NHEJ, in vivo, requires the KU complex, the DNA dependent protein kinase (DNA-PK) and the DNA ligase IV/XRCC4 (LX) complex. In vitro analysis has shown that several linker histone variants are all phosphorylated by DNA-PK. Depletion of a …
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Characterization of a Novel 53BP1-Dependent Mechanism that Promotes Non-Homologous End Joining of Deprotected Telomeres by Increasing Chromatin Mobility
… DSB repair through non-homologous end-joining (NHEJ), the mechanism of their contribution has not been established. To study the regulation of NHEJ, we have used as a model system dysfunctional telomeres, which are uncapped by the removal of the shelterin component, TRF2. As a consequence of …
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53BP1 and double-strand break repair pathway choice in cancer
… choice, promoting non-homologous end-joining (NHEJ) and counteracting homologous recombination (HR). As with all DNA damage response (DDR) proteins, cell-cycle regulation of 53BP1 is critical to its function. The inappropriate activity of 53BP1 in mitosis, during which most of the DDR is …
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